A previous study that investigated the effect of ultrasound (US) on the transdermal permeation of the non-steroidal anti-inflammatory
drug diclofenac found that therapeutic US can increase circulation in an inflamed joint and decrease arthritic
pain. Transdermal
drug delivery has recently been demonstrated by US combined with
microbubbles (MB)
contrast agent (henceforth referred to as "US-MB"). The present study evaluated the efficacy of US-MB-mediated
diclofenac delivery for treating adjuvant-induced
rheumatoid arthritis (RA) in rats. RA was induced by injecting 100 μL of complete
Freund's adjuvant into the ankle joint of male Sprague-Dawley rats (250-300 g) that were randomly divided into five treatment groups: (i)
carbopol gel alone (the control [group C]), (ii)
diclofenac-
carbopol gel (group D), (iii) US plus
carbopol gel (group U), (iv) US plus
diclofenac-
carbopol gel (group DU) and (v) US-MB plus
diclofenac-
carbopol gel (group DUB). The ankle width was measured over 10 d using high-frequency (40-MHz) US B-mode and color Doppler-mode imaging, covering the period before and
after treatment. Longitudinal US images of the induced RA showed
synovitis and neovascularity. Only a small amount of neovascularity was observed
after treatment. The recovery rate on day 10 was significantly higher in group DUB (97.7% ± 2.7%, mean ± standard deviation [SD]) than in groups C (1.0% ± 2.7%), D (37.5% ± 4.6%), U (75.5% ± 4.2%) and DU (87.3% ± 5.2%) (p < 0.05). The results obtained indicate that combining US and MB can increase the skin permeability and thereby enhance the delivery of
diclofenac sodium gel and thereby inhibit
inflammation of the tissues surrounding the arthritic ankle. Color Doppler-mode imaging revealed that US-MB treatment induced a rapid reduction in synovial neoangiogenesis in the arthritic area.